GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease
Seonmi Jo,Seonmi Jo,Oleg Yarishkin,Yu Jin Hwang,Ye Eun Chun,Mijeong Park,Dong Ho Woo,Jin Young Bae,Taekeun Kim,Jaekwang Lee,Heejung Chun,Hyun Jung Park,Da Yong Lee,Jinpyo Hong,Hye Yun Kim,Soo Jin Oh,Seung Ju Park,Hyo Seon Lee,Bo-Eun Yoon,Young-Soo Kim,Yong Jeong,Insop Shim,Yong Chul Bae,Jeiwon Cho,Neil W. Kowall,Neil W. Kowall,Hoon Ryu,Hoon Ryu,Hoon Ryu,Eunmi Hwang,Daesoo Kim,C. Justin Lee +31 more
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TLDR
It is proposed that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.Abstract:
In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.read more
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The Cellular Phase of Alzheimer’s Disease
TL;DR: Evidence supporting a long, complex cellular phase consisting of feedback and feedforward responses of astrocytes, microglia, and vasculature is reviewed.
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Inflammation as a central mechanism in Alzheimer's disease
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TL;DR: An overview of inflammation in AD is provided and a detailed coverage of a number of microglia‐related signaling mechanisms that have been implicated in AD are reviewed.
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Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Fangda Leng,Paul Edison +1 more
TL;DR: The interrelationships between Neuroinflammation and amyloid and tau pathologies as well as the effect of neuroinflammation on the disease trajectory in AD are discussed, focusing on microglia as major players in neuro inflammation and how these cells could be modulated as a therapeutic strategy for AD.
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Reactive astrocyte nomenclature, definitions, and future directions
Carole Escartin,Elena Galea,Andras Lakatos,James P. O'Callaghan,Gabor C. Petzold,Gabor C. Petzold,Alberto Serrano-Pozo,Christian Steinhäuser,Andrea Volterra,Giorgio Carmignoto,Giorgio Carmignoto,Amit Agarwal,Nicola J. Allen,Alfonso Araque,Luis Barbeito,Ari Barzilai,Dwight E. Bergles,Gilles Bonvento,Arthur M. Butt,Wei Ting Chen,Martine Cohen-Salmon,Colm Cunningham,Benjamin Deneen,Bart De Strooper,Bart De Strooper,Blanca Diaz-Castro,Cinthia Farina,Marc R. Freeman,Vittorio Gallo,James E. Goldman,Steven A. Goldman,Steven A. Goldman,Magdalena Götz,Antonia Gutierrez,Philip G. Haydon,Dieter Henrik Heiland,Elly M. Hol,Matthew Holt,Masamitsu Iino,Ksenia V. Kastanenka,Helmut Kettenmann,Baljit S. Khakh,Schuichi Koizumi,C. Justin Lee,Shane A. Liddelow,Brian A. MacVicar,Pierre J. Magistretti,Pierre J. Magistretti,Albee Messing,Anusha Mishra,Anna V. Molofsky,Keith K. Murai,Christopher M. Norris,Seiji Okada,Stéphane H. R. Oliet,João Filipe Oliveira,João Filipe Oliveira,Aude Panatier,Vladimir Parpura,Marcela Pekna,Milos Pekny,Luc Pellerin,Gertrudis Perea,Beatriz G. Pérez-Nievas,Frank W. Pfrieger,Kira E. Poskanzer,Francisco J. Quintana,Richard M. Ransohoff,Miriam Riquelme-Perez,Stefanie Robel,Christine R. Rose,Jeffrey D. Rothstein,Nathalie Rouach,David H. Rowitch,Alexey Semyanov,Alexey Semyanov,Swetlana Sirko,Harald Sontheimer,Raymond A. Swanson,Javier Vitorica,Ina B. Wanner,Levi B. Wood,Jia Qian Wu,Binhai Zheng,Eduardo R. Zimmer,Robert Zorec,Michael V. Sofroniew,Alexei Verkhratsky,Alexei Verkhratsky +88 more
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Journal ArticleDOI
Astrocytes: a central element in neurological diseases
Milos Pekny,Milos Pekny,Milos Pekny,Marcela Pekna,Marcela Pekna,Marcela Pekna,Albee Messing,Christian Steinhäuser,Jin-Moo Lee,Vladimir Parpura,Elly M. Hol,Elly M. Hol,Elly M. Hol,Michael V. Sofroniew,Alexei Verkhratsky +14 more
TL;DR: It is argued that targeting astrocytes may represent an effective therapeutic strategy for Alexander disease, neurotrauma, stroke, epilepsy and Alzheimer’s disease as well as other neurodegenerative diseases.
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